Cancer has overtaken cardiovascular diseases as the leading cause of disease incurred death in the world. In the US over 1 million people get cancer each year, while in China, over 3 million people get cancer each year. 45% of new cancer cases in the world occur in China. The most widely used treatment for cancer is chemotherapy agents, such as taxanes. However, due to taxane's unbearable side effects, including high neutropenia rates (grade 3-4 at 30-40%), its dose has to be decreased during the use or even its use has to be terminated, and thus lowering down its efficacy and treatment duration in cancer patients.
Lung cancer is the leading cause of cancer-related mortality in the United States, China, and the world. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of all cases of lung cancer. By the time most patients are diagnosed with NSCLC, the disease is already advanced. Standard approved therapies for advanced NSCLC generally include successive lines of chemotherapy agents including platins, taxanes, vinca alkyloids, pemetrexed, and/or epidermal growth factor receptor (EGFR) inhibitors.
Docetaxel is a taxane compound approved as second line treatment of NSCLC in the US, European Union, China and multiple other countries. Docetaxel functions by disrupting the microtubule network in cells. It is generally administered as a 1-hour intravenous (IV) infusion once every 3 weeks at a dose of 75 mg/m2 with dexamethasone premedication to minimize the probability of hypersensitivity reactions and fluid retention. In 2 randomized trials with docetaxel in patients with NSCLC previously treated with a platinum-based chemotherapy regimen, the median overall survival (OS) ranged from 5.7 to 7.5 months.
The most common adverse reactions with docetaxel include infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, and etc. Several additional chemotherapeutic agents have been approved as second line therapies for Stage IIIb/IV NSCLC (pemetrexed, erlotinib, and gefitinib), but have clinically equivalent OS outcomes. In wide type NSCLC patients (stage IIIb/IV, second line), OS for docetaxel cohort (75 mg/m2) was 8.2 M, much longer than OS of some other drugs. Thus docetaxel is still the treatment of choice in second line NSCLC treatment.
Since the treatment of cancers is still unsatisfied, there is a clear unmet medical need for additional anti-cancer agents in cancer patients such as those with advanced NSCLC.